This application proposes to conduct randomized, double-blind placebo- controlled trials to test the hypothesis that supplementation with antioxidant vitamins reduces the risk of age-related macular degeneration (AMD) and cataract. This proposal includes continuation of current ongoing investigations conducted as part of the Physicians' Health Study (PHS) and expansion of these studies to include women in the newly established Women's Health Study (WHS). The PHS is a randomized, double-blind, placebo-controlled trial of aspirin use in reducing cardiovascular disease, and beta-carotene in reducing cancer, among 22,071 male U.S. physicians aged 40 to 84 years in 1982. The WHS is a randomized, double- blind, placebo-controlled trial of beta-carotene and vitamin E in the primary prevention of cancer and cardiovascular disease, and low-dose aspirin in the prevention of cardiovascular disease, among over 40,000 female U.S. nurses, aged 50 or older in 1992, with enrollment to begin in the summer of 1992. All self-reports of cataract and AMD will be confirmed by medical record review. The primary aims are to determine through randomized comparisons l) whether beta-carotene supplementation reduces the risk of AMD in men and women, 2) whether beta-carotene supplementation reduces the risk of cataract in men and women, 3) whether vitamin E supplementation reduces the risk of AMD in women, 4) whether vitamin E supplementation reduces the risk of cataract in women, and 5) whether alternate day, low-dose aspirin reduces the risk of cataract in women. It is expected that by the end of the follow-up period there will be approximately 1,660 incident cases of cataract and 600 incident cases of AMD in the PHS, and 1,150 incident cases of cataract and 480 incident cases of AMD in the WHS. The primary analysis for the randomized studies involving beta-carotene, vitamin E, and aspirin treatment will be incidence of AMD or cataract in the treatment and placebo groups. Survival analysis will be used to determine whether there is a difference in time to AMD or cataract diagnosis. The incidence of AMD and cataract will also be investigated prospectively for other antioxidants including vitamins A, C, and E (in men). Other potential risk factors for AMD and cataract which will also be investigated prospectively include systemic hypertension cardiovascular disease, blood cholesterol, blood pressure cigarette smoking, alcohol intake, height body mass index, and diabetes.